Thyroid ultrasonic changes relate to implantation failure in euthyroid women with thyroid autoimmunity undergoing in vitro fertilization/intracytoplasmic sperm injection.

OBJECTIVE: To determine whether ultrasonic manifestations of Hashimoto's thyroiditis (HT) related to embryo qualities or pregnancy outcomes in women with thyroid autoimmunity (TAI) undergoing in vitro fertilization/intracytoplasmic sperm injection. METHODS: Our study was a retrospective cohort study. A total of 589 euthyroid women enrolled from January 2017 to December 2019. 214 TAI women and 375 control women were allocated in each group according to serum levels of thyroid peroxidase antibodies (TPOAb) and/or anti-thyroglobulin antibodies (TgAb). Basal serum hormone levels and thyroid ultrasound were assessed, embryo qualities, pregnancy outcomes were collected from medical records. Diagnosis of thyroid ultrasound was used for subanalysis. Logistic regression was used to evaluate outcomes of embryo development and pregnancy. RESULTS: Implantation rate was significantly lower in euthyroid women with TAI compared with control group (TAI group: 65.5% vs. Control group: 73.0%, adjusted OR (95% CI): 0.65 (0.44, 0.97), p = 0.04). We further stratified TAI group into two groups: one group with HT features under ultrasound and another group with normal thyroid ultrasound. After regression analysis, TAI women with HT morphological changes had a lower chance of implantation compared with control group (TAI group with HT: 64.1% vs. Control group: 73.0%, adjusted OR (95% CI): 0.63 (0.41, 0.99), p = 0.04), while there was no significant difference on implantation rate between TAI women with normal thyroid ultrasound and control group. Other outcomes, such as embryo qualities and pregnancy rate, were comparable between TAI and control groups. CONCLUSIONS: A higher risk of implantation failure was seen among euthyroid women with TAI, especially women with HT morphological changes under ultrasound. The underlying mechanisms of implantation failure among euthyroid HT patients need further research.

The effects of unexpected follicular growth and ovulation in artificial cycles: a retrospective cohort study of frozen, single-blastocyst transfer.

OBJECTIVE: To study the effects of unexpected follicular development and ovulation in artificial cycles (ACs) on pregnancy outcomes. DESIGN: A retrospective cohort study. SETTING: A university-affiliated fertility center. PATIENT(S): A total of 1,427 patients who underwent a single, frozen-thawed blastocyst transfer with AC regimens from January 2014 to December 2020 at a university-affiliated fertility center were included. INTERVENTION(S): Unexpected follicular development and ovulation in ACs. MAIN OUTCOME MEASURE(S): Live birth rate (LBR), biochemical pregnancy rate, clinical pregnancy rate, and ongoing pregnancy rate. RESULT(S): A total of 161 patients with unexpected follicular development and ovulation in ACs (ovulation group) and 1,266 patients without growing follicles in ACs (control group) were enrolled. The patients in the ovulation group were older and had higher levels of serum follicle-stimulating hormone and lower levels of serum antimüllerian hormone. After propensity score matching, the baseline characteristics between the 2 groups were comparable and no significant difference was observed in the LBR (ovulation group, 39.0% vs. control group, 39.0%), biochemical pregnancy rate (ovulation group, 60.3% vs. control group, 58.2%), clinical pregnancy rate (ovulation group, 53.4% vs. control group, 50.7%), or ongoing pregnancy rate (ovulation group, 42.5% vs. control group, 40.4%). Moreover, the patients in the ovulation group showed a lower risk of hypertensive disorders of pregnancy (HDP) (1.6% vs. 15.3%). A subgroup analysis of women who delivered singleton live-born babies also demonstrated that unexpected follicular development and ovulation in ACs was associated with a decreased risk of HDP (adjusted odds ratio, 0.070; 95% confidence interval, 0.007-0.712) and an increased risk of large-for-gestational-age infants (adjusted odds ratio, 4.046; 95% confidence interval, 1.319-12.414). CONCLUSION(S): Women with unexpected follicular development and ovulation during single frozen-thawed blastocyst transfer with AC regimens had a similar LBR and a reduced risk of HDP compared with those with routine AC regimens, and singleton neonates had an increased risk of being large for gestational age.

Association between first-trimester subchorionic hematoma detected at 6-8 weeks of gestation and pregnancy outcomes after fresh embryo transfers: a propensity score-matching cohort study.

PURPOSE: This study aimed to investigate the association between first-trimester subchorionic hematoma (SCH) detected at 6-8 weeks of gestation after fresh embryo transfers and adverse pregnancy outcomes. METHODS: We performed a retrospective cohort involving 3074 patients. All of them acquired singleton pregnancies after fresh embryo transfers in the first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles. According to first-trimester ultrasound examinations at 6-8 weeks of gestation, we divided patients into SCH and non-SCH groups and compared their perinatal outcomes. Symptomatic patients with vaginal bleeding and asymptomatic patients were analyzed separately, and propensity score matching (PSM) and multivariable regression were adopted to control potential confounding factors. RESULTS: The incidence of SCH was 17.1% in 3074 women, and vaginal bleeding occurred in 92 SCH patients and 215 control patients. In the asymptomatic cohort, 415 women with SCH and 807 women without SCH were finally included after PSM. No significant differences were observed in livebirth rate (91.3% vs 92.9%, P = 0.314), miscarriage rate (8.4% vs 6.7%, P = 0.267), and preterm birth rate (4.8% vs 5.7%, P = 0.519) between two groups. Secondary outcomes including gestational hypertension or preeclampsia, gestational diabetes mellitus (GDM), gestational age (GA) at delivery, mode of delivery, sex of newborns and birthweight of newborns were comparable. For symptomatic patients, both univariable and multivariable regression analysis showed no significant association between SCH and pregnancy outcomes. A subgroup analysis including patients with SCH illustrated the symptom of vaginal bleeding rather than hematoma size was associated with livebirth. CONCLUSION: First-trimester SCH detected at 6-8 weeks of gestation was not associated with adverse pregnancy outcomes in singleton pregnancies after fresh embryo transfers. Vaginal bleeding was the risk factor of pregnancy loss for patients with SCH.

Lung-protective Ventilation in Patients with Brain Injury: A Multicenter Cross-sectional Study and Questionnaire Survey in China.

BACKGROUND: Over the years, the mechanical ventilation (MV) strategy has changed worldwide. The aim of the present study was to describe the ventilation practices, particularly lung-protective ventilation (LPV), among brain-injured patients in China. METHODS: This study was a multicenter, 1-day, cross-sectional study in 47 Intensive Care Units (ICUs) across China. Mechanically ventilated patients (18 years and older) with brain injury in a participating ICU during the time of the study, including traumatic brain injury, stroke, postoperation with intracranial tumor, hypoxic-ischemic encephalopathy, intracranial infection, and idiopathic epilepsy, were enrolled. Demographic data, primary diagnoses, indications for MV, MV modes and settings, and prognoses on the 60th day were collected. Multivariable logistic analysis was used to assess factors that might affect the use of LPV. RESULTS: A total of 104 patients were enrolled in the present study, 87 (83.7%) of whom were identified with severe brain injury based on a Glasgow Coma Scale ≤8 points. Synchronized intermittent mandatory ventilation (SIMV) was the most frequent ventilator mode, accounting for 46.2% of the entire cohort. The median tidal volume was set to 8.0 ml/kg (interquartile range [IQR], 7.0-8.9 ml/kg) of the predicted body weight; 50 (48.1%) patients received LPV. The median positive end-expiratory pressure (PEEP) was set to 5 cmH2O (IQR, 5-6 cmH2O). No PEEP values were higher than 10 cmH2O. Compared with partially mandatory ventilation, supportive and spontaneous ventilation practices were associated with LPV. There were no significant differences in mortality and MV duration between patients subjected to LPV and those were not. CONCLUSIONS: Among brain-injured patients in China, SIMV was the most frequent ventilation mode. Nearly one-half of the brain-injured patients received LPV. Patients under supportive and spontaneous ventilation were more likely to receive LPV. TRIAL REGISTRATION: ClinicalTrials.org NCT02517073 https://clinicaltrials.gov/ct2/show/NCT02517073.

STMN1 Promotes Progesterone Production Via StAR Up-regulation in Mouse Granulosa Cells.

Stathmin 1 (STMN1) is a biomarker in several types of neoplasms. It plays an important role in cell cycle progression, mitosis, signal transduction and cell migration. In ovaries, STMN1 is predominantly expressed in granulosa cells (GCs). However, little is known about the role of STMN1 in ovary. In this study, we demonstrated that STMN1 is overexpressed in GCs in patients with polycystic ovary syndrome (PCOS). In mouse primary GCs, the overexpression of STMN1 stimulated progesterone production, whereas knockdown of STMN1 decreased progesterone production. We also found that STMN1 positively regulates the expression of Star (steroidogenic acute regulatory protein) and Cyp11a1 (cytochrome P450 family 11 subfamily A member 1). Promoter and ChIP assays indicated that STMN1 increased the transcriptional activity of Star and Cyp11a1 by binding to their promoter regions. The data suggest that STMN1 mediates the progesterone production by modulating the promoter activity of Star and Cyp11a1. Together, our findings provide novel insights into the molecular mechanisms of STMN1 in ovary GC steroidogenesis. A better understanding of this potential interaction between STMN1 and Star in progesterone biosynthesis in GCs will facilitate the discovery of new therapeutic targets in PCOS.

[Correlation analysis between polycystic ovary syndrome susceptibility genes and metabolic phenotypes].

OBJECTIVE: To investigate the relationship between polycystic ovary syndrome (PCOS) susceptibility single nucleotide polymorphisms (SNP) and metabolic phenotypes in glucose and lipid metabolism and explore the pathophysiological mechanism of the susceptibility genes. METHODS: Three of PCOS susceptibility locus 2p16.3 (rs13405728 of LHCGR gene), 2p21 (rs13429458, rs12478601 of THADA gene) and 9q33.3 (rs2479106, rs10818854 of DENNDIA gene) were selected and the metabolic phenotypes were compared between different genotypes of SNP in PCOS patients (using dominant model). RESULTS: Low-density lipoprotein cholesterol was significantly increased in CC genotype group than in TC + TT groups at rs12478601 of THADA gene [(2.5 ± 0.8), (2.4 ± 0.8) mmol/L; P = 0.01]. Serum insulin level of 2 hours after 75 g glucose intake was significantly higher in GG+AG groups than that of AA group at rs2479106 of DENND1A gene[(71 ± 65), (64 ± 50) mU/L; P = 0.05 ], and the prevalence of type II diabetes in first-degree relatives of patients were also increased [9.9% (66/666), 6.9% (52/751); P < 0.05]. No association was found between metabolic phenotypes and genotypes of rs13429458, rs10818854, and rs13405728. CONCLUSIONS: Genetic factors probably have effect on the metabolic characteristics of PCOS. THADA gene is related to lipid metabolism, while DENND1A gene may be involved in insulin metabolism in patients with PCOS.

Hypertension in women with polycystic ovary syndrome: prevalence and associated cardiovascular risk factors.

OBJECTIVE: To determine the prevalence of hypertension in women with polycystic ovary syndrome (PCOS). STUDY DESIGN: Women with PCOS (n=3396) and controls (n=1891) from a Han Chinese population were analysed retrospectively in terms of ovarian appearance on ultrasound, glucose tolerance test, hormones, lipoproteins, anthropomorphic measurements and blood pressure. RESULTS: The prevalence of hypertension was 19.2% in the women with PCOS, which was much higher than that in the controls (11.9%). After matching for body mass index, the hypertensive PCOS group had higher glucose, insulin, homeostatic model assessment (HOMA-IR) and lipid levels than the normotensive PCOS group; these differences were significant (p<0.05). CONCLUSIONS: Hypertensive PCOS patients had higher lipid, insulin and glucose levels than normotensive PCOS patients. It is likely that the incidence of long-term complications will be higher among the former group.

[Effect of obesity on nonalcoholic fatty liver disease in Chinese women with polycystic ovary syndrome].

OBJECTIVE: To investigate the effect of obesity on nonalcoholic fatty liver disease (NAFLD) in women with polycystic ovary syndrome (PCOS). METHODS: The patient data were acquired from 306 women with PCOS by Rotterdam consensus criteria and 286 women selected as controls. Basal endocrine, oral glucose tolerance test (OGTT), insulin release test, lipid profile, blood pressure and body mass index (BMI) were tested. The essays of liver chemistries, B-hepatitis and c-hepatitis were performed and alcoholic liver diseases excluded. Fatty liver was diagnosed by ultrasound. RESULTS: Patients with PCOS showed a higher prevalence of NAFLD than control group (30.7% vs 17.5%), including 56 mild cases (59.6%), 34 moderate cases (36.2%) and 4 severe cases (4.2%). The prevalence of NAFLD in PCOS increased with BMI, waist hip ratio, triglyceride and HOMA-IR. The prevalence of NAFLD in abdominal obese PCOS patients was significantly higher than those with normal waist. In addition to the prevalence of insulin resistance, metabolic syndrome in PCOS women significantly increased with BMI. CONCLUSION: These findings indicate that Chinese women with PCOS have a high prevalence of NAFLD, especially in abdominal and II obese PCOS patients. The prevalence and severity of NAFLD are positively correlated with BMI. It seems that insulin resistance and metabolic abnormalities are closely associated with NAFLD in PCOS. It is essential to give a high priority to the screening and treatment of NAFLD in obese PCOS patients.

[Clinical analysis of assistant treatment proposals for infertile women with polycystic ovary syndrome].

OBJECTIVE: To study the clinical outcomes of assistant treatment proposals for infertile women with polycystic ovary syndrome (PCOS). METHODS: PCOS patients were divided into four groups according to the assistant treatment proposals between Jan 2003 and Dec 2007 in Reproductive Medicine Center of the Provincial Hospital Affiliated to Shandong University. The four proposals were letrozole (LE) or clomiphene (CC) citrate ovulation induction group, in vitro fertilization and embryo transplantation group, ultrasound-guided immature follicle puncture group, and in vitro maturation and fertilization of oocytes from unstimulated cycles group. The treatment results were analyzed. RESULTS: (1) The ovulation rate was 66% (38/58) vs 47% (21/45). The mean endometrial thickness [(0.89 +/- 0.13) vs (0.78 +/- 0.08) cm] and cervical mucus score (11.9 +/- 1.8 vs 9.9 +/- 1.8) on the day of human chorionic gonadotropin (hCG) administration in LE group were both higher than that in CC group, while mature follicle (1.08 +/- 0.28 vs 1.73 +/- 0.59) and serum estradiol level [(983 +/- 138) vs (1676 +/- 372) pmol/L] in LE group were lower than that in CC group (P < 0.05). (2) One southend five hundred and eighty-four patients accepted in vitro fertilization-embryo transplantation therapy because of PCOS (PCOS group) and 1615 patients because of tube factors (control group). The patients' ages and infertility years were matched between the two groups. Total doses of Gn [(980 +/- 1192) vs (1194 +/- 1389) IU] of PCOS group were lower than those of control group. The mean days of using gonadotropin [(9.6 +/- 1.8) vs (9.5 +/- 1.8) d], serum estradiol (E(2)) levels on the hCG day [(15 752 +/- 6206) vs (9675 +/- 4818) pmol/L], mean obtained oocytes (21 +/- 6 vs 9 +/- 3), mean fertilized oocytes (15 +/- 6 vs 7 +/- 3) and mean cleavaged oocytes (12.9 +/- 5.7 vs 5.7 +/- 2.8) of PCOS group were higher than those of the control group (P < 0.05). Moderate and severe ovarian hyperstimulation syndrome (OHSS) rates (4.86% vs 1.67%) of PCOS group were higher than that of the control group. The pregnant rate (44.7% vs 45.0%)of PCOS group was similar to the control group (P > 0.05). (3) One hundred and nine PCOS patients were given ultrasound-guided immature follicle puncture therapy. After treatment, the testosterone level, luteinizing hormone (LH) level and LH/follicle stimulating hormone (FSH) ratio of the patients became normal. The basic follicle number decreased. (4) A total of 304 in vitro maturation cycles were performed. After embryo transfer, 76 pregnancies were reported. CONCLUSIONS: There are many choices for the infertile patients with PCOS, such as LE or CC citrate ovulation induction, in vitro fertilization and embryo transplantation, ultrasound-guided immature follicle puncture, and in vitro maturation and fertilization of oocytes from unstimulated cycles. We can provide individualized treatment according to the medical treatment conditions, doctors' professional capability and the patients' situation.

[Analysis of therapeutic outcomes of polycystic ovary syndrome patients with hyperprolactinemia].

OBJECTIVE: To study effect of drug treatment in polycystic ovary syndrome patients with hyperprolactinemia. METHODS: We retrospectively studied 63 women with polycystic ovary syndrome and hyperprolactinemia from the Reproductive Medicine Center, Provincial Hospital between January 2005 and March 2007. According to the beginning time of bromocriptine, all women were divided into two groups. Group I was composed of 48 cases who received bromocriptine administration before induction of ovulation cycles, and the dose of bromocriptine was modulated depending on the level of serum prolactin. When serum prolactin was controlled at normal levels, we decreased the dosage of bromocriptine step by step (1.25 mg once), and then continued the treatment at maintenance dosage for no less than 3 weeks. After a baseline ultrasonographic examination on day 3, patients were treated with clomiphene citrate at a dosage of 100 mg (2 tablets/day) for 5 days of a normal cycle or progesterone-induced bleeding. On day 9, we monitored the growth conditions of follicles routinely with trans-vaginal ultrasound. If there was no dominant follicle, we added human menopausal hormone (hMG, 75 U/d) to the protocol. Human chorionic gonadotropin (hCG, 6000-10,000 IU) was given intramuscularly when the mean diameter of a follicle reached at least 18 mm. At the same time we instructed the patients to have sexual intercourses or carried out artificial inseminations before and after ovulation. Group II were 15 cases in which induction of ovulations were commenced almost simultaneously with beginning of bromocriptine. The same protocol was given to patients in group II. The procedures of ovulation induction and the outcomes of treatment were analyzed and compared. RESULTS: Compared with group II , the days of using hMG in Group I was shorter by instructing the time of sexual intercourse. The difference was significant (P = 0.004). And there were similar results in the artificial insemination cycles (P = 0.009). The rate of pregnancy in group I (40%, 19/48) was higher than that in group II (27%, 4/15), but the difference was not obvious (P = 0.525 ). CONCLUSION: Bromocriptine administration before the stimulated ovulation therapy can decrease the total dosage and treatment course of ovulating drugs. Induction of ovulations simultaneously with start of bromocriptine therapy can shorten the treatment time of infertility.

[Investigation of body hair assessment of Chinese women in Shandong region and its preliminary application in polycystic ovary syndrome patients].

OBJECTIVE: To determine a suitable standard of hirsutism for Chinese polycystic ovary syndrome (PCOS) patients living in Shandong region. METHODS: A total of 623 unbiased women from the general population in Jinan city, 131 PCOS patients and 84 controls from outpatients in Shandong region were studied with questionnaires, physical and pelvic ultrasound examination, body hair on 11 sites were evaluated, and 9 (lip, chin, arm, thigh, chest, upperbelly, lowerbelly, upperback, lowback) of them which were called hormone Ferriman-Gallwey (F-G) score and 2 (forearm, leg) sites of indifferent hormone score were calculated according to the score system described by Ferriman and Gallwey. RESULTS: (1) Both body hair F-G score and indifferent hormone score distribution mode in the or= 2 (chi(2) = 47.68, P < 0.01), but no statistic difference by F-G score >or= 6 criterion (chi(2) = 0.64, P = 0.42). (3) F-G scores were declined with age increase. The hair score on the lip, chest, lowerbelly in general population were positively correlated with F-G score (r = 0.712, 0.594, 0.522; P < 0.01) and in PCOS patients (r = 0.879, 0.682, 0.710; P < 0.01), and on the lip in controls (r = 0.950, P < 0.01). (4) The correlation contingency coefficient between hirsutism (F-G score >or= 2) and lip, chest, lowerbelly site in general population was 0.461, 0.420, 0.489 and was 0.560, 0.532, 0.503 in PCOS group respectively. CONCLUSIONS: (1) Both body hair F-G score and indifferent hormone score distribution mode are significantly different from Ferriman-Gallwey's report; according to our investigation the suitable criterion of hirsutism for Chinese women in Shandong region should be >or= 2 scores. (2) By F-G score >or= 2 standard, hirsutism is more common in PCOS than in control. (3) Lip, chest, and lowerbelly are the main sites to determine the hirsutism status of women, and the later two sites are more specific for PCOS hirsutism. Forearm and leg score can indicate hirsutism status in some degree but are not specific and sensitive for PCOS hirsutism.

[Correlation between 4G and 5G genetypes distribution of plasminogen activator inhibitor-1 gene polymorphism in its promoter region with polycystic ovarian syndrome].

OBJECTIVE: To investigate the correlation of 4G and 5G genetypes distribution of plasminogen activator inhibitor-1 (PAI-1) gene polymorphism in its promoter region with polycystic ovary syndrome (PCOS). METHODS: In 101 Chinese PCOS patients and 42 women as control, 4G and 5G polymorphisms of PAI-1 gene were detected with PCR-restriction fragment length polymorphism (RFLP). Pregnant history, body mass index (BMI), waist-hip ratio (WHR) were collected and Homastasis Model Assessment score for insulin resistant (Homa-IR) and insulin sensitive index (ISI) in PCOS groups were calculated. RESULTS: The distributions of PAI-1 gene polymorphisms 4G type (4G/4G genetype) and 5G type (5G/5G, 4G/5G genetype) were different between the PCOS group and the control. The PCOS group had higher 4G type 57% (58/101) distribution than that of the control group 38% (16/42); 5G type is vise verse (P < 0.05). PCOS patients were divided into obese and non-obese sub-groups according to BMI. There were significant lower Homa-IR and higher ISI in non-obese subgroup than that in obese group (P < 0.05; P < 0.01). 68% (36/53) 4G type distribution in the non-obese is higher than that [48% (23/48)] in obese sub-group (P < 0.05). There were higher 4G type distribution 79% (11/14) and lower 5G type distribution 21% (3/14) in spontaneous miscarriage group than that of in non-spontaneous miscarriage group 38% (5/13) and 62% (8/13) among patients who impregnated at least once (n = 27, P < 0.05). CONCLUSION: PAI-1 gene polymorphism 4G genetype may be correlated with PCOS in Chinese women, especially in PCOS patients with non-obese PCOS and spontaneous miscarriage.